A Transcriptome Analysis: Various Reasons of Adverse Pregnancy Outcomes Caused by Acute Toxoplasma gondii Infection

Xue Zhou; Xiu-Xiang Zhang; Yasser S Mahmmod; Jorge A Hernandez; Gui-Feng Li; Wan-Yi Huang; Ya-Pei Wang; Yu-Xiang Zheng; Xiu-Ming Li; Zi-Guo Yuan

doi:10.3389/fphys.2020.00115

A Transcriptome Analysis: Various Reasons of Adverse Pregnancy Outcomes Caused by Acute Toxoplasma gondii Infection

Front Physiol. 2020 Feb 19:11:115. doi: 10.3389/fphys.2020.00115. eCollection 2020.

Authors

Xue Zhou^{1

2

3}, Xiu-Xiang Zhang⁴, Yasser S Mahmmod^{5

6

7}, Jorge A Hernandez⁸, Gui-Feng Li^{1

2

3}, Wan-Yi Huang^{1

2

3}, Ya-Pei Wang^{1

2

3}, Yu-Xiang Zheng^{1

2

3}, Xiu-Ming Li⁹, Zi-Guo Yuan^{1

2

3}

Affiliations

¹ College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
² Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China.
³ Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, China.
⁴ College of Agriculture, South China Agricultural University, Guangzhou, China.
⁵ IRTA, Centre de Recerca en Sanitat Animal, Barcelona, Spain.
⁶ Universitat Autónoma de Barcelona, Barcelona, Spain.
⁷ Infectious Diseases, Department of Animal Medicine, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁸ College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
⁹ College of Animal Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China.

Abstract

Background: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite, which can affect the pregnancy outcomes in infected females by damaging the uterus, and the intrauterine environment as well as and the hypothalamus resulting in hormonal imbalance. However, the molecular mechanisms underlying the parasite-induced poor pregnancy outcomes and the key genes regulating these mechanisms remain unclear. Therefore, this study aimed to analyze the gene expression in the mouse's uterus following experimentally-induced acute infection with T. gondii RH strain. Three groups of female mice were intraperitoneally injected with tachyzoites as follow; 3 days before pregnancy (FBD6), after pregnancy (FAD6), and after implantation (FID8) as the experimental groups. Another corresponding three groups served as control, were injected with normal saline at the same time. Transcriptome analysis of the total RNA extracted from both infected and non-infected mouse uterus samples was performed using RNA sequencing (RNA-Seq).

Results: The three experimental groups (FBD6, FAD6, and FID8) had a total of 4,561, 2,345, and 2,997 differentially expressed genes (DEGs) compared to the controls. The significantly upregulated and downregulated DEGs were 2,571 and 1,990 genes in FBD6, 1,042 and 1,303 genes in FAD6 and 1,162 and 1,835 genes in FID8 group, respectively. The analysis of GO annotation, and KEGG pathway showed that DEGs were mainly involved in anatomical structure development, transport, cell differentiation, embryo development, hormone biosynthetic process, signal transduction, immune system process, phagosome, pathways in cancer, and cytokine-cytokine receptor interaction pathways.

Conclusion: T. gondii infection can induce global transcriptomic changes in the uterus that may cause pregnancy hypertension, destruct the intrauterine environment, and hinder the normal development of placenta and embryo. Our results may help to understand the molecular mechanisms of the acute T. gondii infection, which could promote the development of new therapeutics or prophylactics for toxoplasmosis in pregnancy.

Keywords: DEGs; RNA-Seq; T. gondii; abnormal pregnancy; acute infection.